Use of the Intratumoural Anticancer Drug Tigilanol Tiglate in Two Horses

Ridder, Thomas R De; Ruppin, Mick; Wheeless, Meagan; Williams, Simon; Reddell, Paul

doi:10.3389/fvets.2020.00639

Cited by 13 publications

(14 citation statements)

References 11 publications

(28 reference statements)

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“…Examples of the progression of wound healing after slough of MCTs on lower limbs (at or below the elbow and hock) that had received a single treatment with TT. Case 01-012 (A-D) was treated in phase 2 of the study with a 0.5 cm 3 MCT at time of treatment and a maximal wound of 5.3 cm 2 was recorded after tumor slough. Case 06-008 (E-H) was treated in phase 1 of the study with a 1.9 cm 3…”

Section: F I G U R Ementioning

confidence: 99%

“…Case 01-012 (A-D) was treated in phase 2 of the study with a 0.5 cm 3 MCT at time of treatment and a maximal wound of 5.3 cm 2 was recorded after tumor slough. Case 06-008 (E-H) was treated in phase 1 of the study with a 1.9 cm 3…”

Section: F I G U R Ementioning

confidence: 99%

“…The drug is also in broader clinical development for a range of other cutaneous and subcutaneous cancers in humans, 1,2 companion animals, and horses. 3 A previous report 4 underlying wound bed of healthy granulation tissue up to 14 days after treatment. 4,6 Here we present further results from that clinical study.…”

Section: Introductionmentioning

confidence: 98%

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Wound formation, wound size, and progression of wound healing after intratumoral treatment of mast cell tumors in dogs with tigilanol tiglate

Reddell¹,

Ridder²,

Morton³

et al. 2021

Veterinary Internal Medicne

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Background: Tigilanol tiglate (TT) is a novel small molecule for intratumoral treatment of nonmetastatic mast cell tumors (MCTs) in dogs. In a randomized controlled clinical study, 75% of dogs that received a single TT treatment achieved complete resolution of the MCT by 28 days, with no recurrence in 93% of dogs at 84 days. Critical to TT's efficacy was the area of the wound (tissue deficit) after slough of the necrotic tumor relative to pretreatment tumor volume. Objectives: To analyze data collected during the previous study to (a) describe wounds after slough of treated MCTs and (b) identify determinants of wound area and speed of wound healing. Methods: Wound presence, condition, and area were determined from clinical records of 117 dogs over 84 days after a single intratumoral TT treatment. Results: Tumor slough occurred 3 to 14 days after treatment, exposing granulation tissue in the wound bed. Wound area after tumor slough in general was related to pretreatment tumor volume, with maximal recorded wound area fully evident in 89% of dogs by day 7. In dogs achieving complete tumor resolution, all wounds were left to heal by secondary intention. Bandaging and other wound management interventions only were required in 5 dogs. Time to healing (ie, full re-epithelialization of treatment site) depended on wound area and location on the body, with most wounds being fully healed between 28 and 42 days after treatment. Conclusions: Wound area and healing after slough of TT-treated tumors follow a consistent clinical pattern for most dogs.

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Section: F I G U R Ementioning

confidence: 99%

Section: F I G U R Ementioning

confidence: 99%

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Wound formation, wound size, and progression of wound healing after intratumoral treatment of mast cell tumors in dogs with tigilanol tiglate

Reddell¹,

Ridder²,

Morton³

et al. 2021

Veterinary Internal Medicne

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“…Diterpenes exhibit many and varied biological activities and consequently there is significant commercial interest in their potential applications as pharmaceuticals, food products, and industrial and agricultural chemicals [ 1 – 5 ]. Tigilanol tiglate (TT), a novel epoxy-tigliane diterpene ester extracted from the fruit of Fontainea picrosperma (family Euphorbiaceae) [ 3 , 6 ], is of particular current interest due to its effectiveness as a local treatment for a range of cancers in humans and companion animals [ 3 , 7 – 9 ]. Recently, TT was approved by regulatory authorities in Europe and the USA as a veterinary pharmaceutical for the treatment of non-metastatic canine mast cell tumours.…”

Section: Introductionmentioning

confidence: 99%

The P450 multigene family of Fontainea and insights into diterpenoid synthesis

et al. 2021

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Background Cytochrome P450s (P450s) are enzymes that play critical roles in the biosynthesis of physiologically important compounds across all organisms. Although they have been characterised in a large number of plant species, no information relating to these enzymes are available from the genus Fontainea (family Euphorbiaceae). Fontainea is significant as the genus includes species that produce medicinally significant epoxy-tigliane natural products, one of which has been approved as an anti-cancer therapeutic. Results A comparative species leaf metabolome analysis showed that Fontainea species possess a chemical profile different from various other plant species. The diversity and expression profiles of Fontainea P450s were investigated from leaf and root tissue. A total of 103 and 123 full-length P450 genes in Fontainea picrosperma and Fontainea venosa, respectively (and a further 127/125 partial-length) that were phylogenetically classified into clans, families and subfamilies. The majority of P450 identified are most active within root tissue (66.2% F. picrosperma, 65.0% F. venosa). Representatives within the CYP71D and CYP726A were identified in Fontainea that are excellent candidates for diterpenoid synthesis, of which CYP726A1, CYP726A2 and CYP71D1 appear to be exclusive to Fontainea species and were significantly more highly expressed in root tissue compared to leaf tissue. Conclusion This study presents a comprehensive overview of the P450 gene family in Fontainea that may provide important insights into the biosynthesis of the medicinally significant epoxy-tigliane diterpenes found within the genus.

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“…Diterpenes exhibit many and varied biological activities and consequently there is signi cant commercial interest in their potential applications as pharmaceuticals, food products, and industrial and agricultural chemicals [1][2][3][4][5]. Tigilanol tiglate (TT), a novel epoxy-tigliane diterpene ester extracted from the fruit of Fontainea picrosperma (family Euphorbiaceae) [3,6], is of particular current interest due to its effectiveness as a local treatment for a range of cancers in humans and companion animals [3,[7][8][9]. Recently, TT was approved by regulatory authorities in Europe and the USA as a veterinary pharmaceutical for the treatment of non-metastatic canine mast cell tumours.…”

Section: Introductionmentioning

confidence: 99%

The CYP450 Multigene Family of Fontainea and Insights Into Diterpenoid Synthesis

Mitu

Ogbourne

Klein

et al. 2021

Preprint

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Background: Cytochrome P450s (CYP450s) are enzymes that play critical roles in the biosynthesis of physiologically important compounds across all organisms. Although they have been characterised in a large number of plant species, no information relating to these enzymes are available from the genus Fontainea (family Euphorbiaceae). Fontainea is significant as the genus includes species that produce medicinally significant epoxy-tigliane natural products, one of which has been approved as an anti-cancer therapeutic. Results: A metabolome analysis showed that Fontainea species possess a chemical profile different from various other plant species. The diversity and expression profiles of Fontainea CYP450s were investigated from leaf and root tissue. A total of 103 and 123 full-length CYP450 genes in Fontainea picrosperma and Fontainea venosa, respectively (and a further 127/125 partial-length) that were phylogenetically classified into clans, families and subfamilies. The majority of CYP450 identified are most active within root tissue (66.2% F. picrosperma, 65.0% F. venosa). Fontainea CYP450 associated with diterpenoid biosynthesis were classified into 2 subfamilies (CYP71D and CYP726A), of which CYP726A1, CYP726A2 and CYP71D1 appear to be exclusive to Fontainea species, and significantly more highly expressed in root tissue compared to leaf tissue. Conclusion: This study presents a comprehensive overview of the CYP450 gene family in Fontainea that may provide important insights into the biosynthesis of the medicinally significant epoxy-tigliane diterpenes found within the genus.

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Use of the Intratumoural Anticancer Drug Tigilanol Tiglate in Two Horses

Cited by 13 publications

References 11 publications

Wound formation, wound size, and progression of wound healing after intratumoral treatment of mast cell tumors in dogs with tigilanol tiglate

Wound formation, wound size, and progression of wound healing after intratumoral treatment of mast cell tumors in dogs with tigilanol tiglate

The P450 multigene family of Fontainea and insights into diterpenoid synthesis

The CYP450 Multigene Family of Fontainea and Insights Into Diterpenoid Synthesis

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